The sequelae of biochemical, cellular, and/or molecular events leading to the development of age-related macular degeneration (AMD), the leading cause of irreversible blindness in this country, are poorly understood. Aims outlined in this proposal are directed toward continued morphological and molecular characterization of drusen, BLD, and Bruch's membrane, based on the general operating hypothesis that knowledge pertaining to the composition of these structures will provide insight into the pathobiology of AMD. Other aims will test the hypothesis that RPE "injury" and immune-mediated processes are intimately involved in early drusen biogenesis and, by extension, in the development of AMD. The specific identity of previously undescribed drusen-associated choriodal monocytes will be established. Additional aims will address a hypothesis predicting that the macula is more susceptible to degeneration in AMD because the structure and composition of Bruch's membrane in this region is different than that of extramacular regions. We anticipate that these foundational studies will continue to provide new knowledge about the pathobiology of drusen, BLD, Bruch's membrane, and the RPE that will contribute to a conceptual framework for pursuing additional basic and clinical research into the causes and prevention of AMD.